DESCRIPTION: See instructions. State the application's broad, long-term objectives and specific aims, making referenceto the health relatedness of the project (i.e., relevance to the mission of the agency). Describe concisely the research design and methods for achieving these goals. Describe the rationale and techniques you will use to pursue these goals. In addition, in two or three sentences, describe in plain, lay language the relevance of this research to public health. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED THE SPACE PROVIDED. Project Summary. Cell adhesion is governed by interactions of cell surface receptors with proteins found in the extracellular matrix (ECM). Nanometer and micrometer length scales are relevant in this process, and flexible strategies to pattern cell adhesion ligands derived from ECM proteins, particularly at the micro- and nanoscale, provides tremendous opportunities to study and control cell behavior. One objective of this research is to employ ultraviolet (UV) irradiation to selectively chemically transform programmable polymer surfaces to micropattern cell adhesion peptides. A second objective is to translate the technology using low intensity electron beam (e-beam) radiation to fabricate nanopatterns of peptides. We hypothesize that micropatterns and nanopatterns of cell adhesion peptides fabricated using UV or e-beam radiation and a pH- sensitive polymer surface will promote cell adhesion. We have proposed two specific aims to reach our objectives. The first aim is to quantify osteoblast behavior on surfaces micropatterned with cell adhesion peptides. Polymer surfaces will be prepared and subsequently converted to micropatterns of amine-reactive groups using UV light, a photoacid generator (PAG), and a mask. Cell adhesion peptides will be conjugated to the surfaces. In vitro cell culture will verify that the surfaces promote osteoblast adhesion, proliferation, and differentiation. The second aim is to fabricate nanoarrays of biomolecules using pH sensitive surfaces. Nanopatterns of biomolecules will be generated using e-beam radiation. Osteoblast adhesion will be demonstrated to validate the approach. One potential outcome of this research is the development of new implant coatings that promote osseointegration. The second potential outcome is a general strategy to pattern biomolecules with nanometer resolution to study cell adhesion. The long-term goal of this research is to employ a flexible patterning technique to determine the critical sizes, shapes, and physical separations of cell adhesion ligands at the nanoscale. Such information is essential to the rational design of biomaterials and to understanding the mechanisms by which signals from the ECM are transduced to the cell interior. Relevance. Surface coatings that promote and control cell behavior can lead to better human implants and devices. PERFORMANCE SITE(S) (organization, city, state) University of California, Los Angeles, CA PHS 398 (Rev. 09/04) Page 2 Form Page 2 Principal Investigator/Program Director (Last, First, Middle): Maynard, Heather Dawn KEY PERSONNEL. See instructions. Use continuation pages as neededto provide the required information in the format shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name eRA Commons User Name Organization Role on Project Maynard, Heather D. maynard UCLA Principalinvestigator Chen, Yong UCLA Co-investigator OTHER SIGNIFICANT CONTRIBUTORS Name Organization Role on Project Wu, Benjamin M. UCLA Consultant Human Embryonic Stem Cells ^ No Q Yes If the proposed project Involves human embryonic stem cells, list below the registration number of the specific cell line(s) from the following list: http://StemcellS.nih.gov/registry/index.asp. Usecontinuation pages as needed. If a specific line cannot be referenced at this time, include a statement that one from the Registry will be used. Cell Line Disclosure Permission Statement. Applicable to SBIR/STTR Only. See SBIR/STTR instructions. L~H Yes EH No PHS 398 (Rev. 09/04) Page 3 Form Page 2-contlnued Number the following pages consecutively throughout the application. Do not use suffixes such as 4a, 4b. Principal Investigator/Program Director (Last, First, Middle): MayiWd, Heather Dawn The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT